Amides, from acid derivatives nitration

Nitronate(47a) is not the only oxazete derivative. For example, sterically hindered nitroalkenes (42b-d) can be prepared by nitration and halogenation of readily available allenes (48). Compounds (42b-d) are rather smoothly isomerized into the corresponding four-membered cyclic nitronates (47b-d) by the first-order reaction equation (168). Storage of nitronate (47c) is accompanied by its slow transformation into acid chloride (47e) from which amide (47f) can be easily synthesized. 

Feuer and co-workers ° conducted extensive studies into alkaline nitration with nitrate esters, exploring the effect of base, time, stoichiometry, concentration, solvent, and temperature on yields and purity. Reactions are generally successful when the substrate a-proton acidity is in the 18-25 p A a range. Alkoxide bases derived from simple primary and secondary aliphatic alcohols are generally not considered compatible in reactions using alkyl nitrates. Optimum conditions for many of these reactions use potassium tert-butoxide and amyl nitrate in THF at —30 °C, although in many cases potassium amide in liquid ammonia at —33 °C works equally well. 

A number of reagents derived from nitrate salts and acid anhydrides have been reported for the V-nitration of amides and related compounds. Crivello first reported the use of metal nitrates in trifluoroacetic anhydride (TFAA) for the nitration of aromatic systems. Chapman... 

The total synthesis of ( + )-Erysotramidine (2) has been described by Ito et al. (137) starting from the amide (174) (Scheme 39). After O-mesylation to 177, base-catalyzed reaction gave the cyclopropane derivative (178) which with zinc in acetic acid was reduced to 179, which was identical to the product (135) of O-methylation of 172. Conversion of 178 to the thioketal (180) was followed by reaction with phenylselenyl chloride. A mixture of two compounds, 181 and 182, was produced the former could be transformed quantitatively to the latter. Finally, treatment of 182 with silver nitrate in methanol gave 183, which was then desulfurized to yield erysotramidine (2). 

This yields a manobenzoyl derivative, crystallising from 50 per cent, alcohol in lustrous, hexagonal plates, undecomposed below 290° C. The free acid is identical with that prepared by nitrating phenyl-arsinie acid 4-glycine-amide and reducing the nitro-acid with ferrous hydroxide. 

The acyloxylation of A -alkylsubstituted amides has received considerable attention [70,75,118], from both the mechanistic and the preparative points of view. In electrolytes containing alkali metal carboxylates the direct mechanisms probably operates, whereas in the case where a nitrate salt is the supporting electrolyte an indirect mechanism involving hydrogen abstraction from the A -alkyl group by anodically generated NO3 is indicated. The same mechanistic problem is encountered in side-chain acetoxylation of alkylaromatic compounds in the presence of N03 [123,152,153]. The method for large-scale substitution into A -formyl derivatives, which works so well for methoxylation, fails when applied to acetoxylation, probably because of the acid sensitivity of the products [80]. 

The ammonium salt which results from the transformation of sulfuryl amide can be converted to a silver salt, AgNSO ELO, by silver nitrate (64) and this readily gives AgNS02. The silver salt with methyl iodide yields the N-methyl derivative (LXXI) (61). Since molecular weight determinations show the methyl derivative to be a trimer, it may also be assumed that the salts, and particularly that of silver, are also trimeric. Attempts to isolate the hydrogen compound (LXIX) have so far failed, but Heinze and Meuwsen (64) have prepared many salts of (LXIX). They also were able to show that when the silver salt was decomposed with an equivalent quantity of hydrochloric acid a tribasic acid resulted which was to some extent stable in water. It readily lost two protons, but one proton was split off only with difficulty. The ion (LXX) clearly has a high stability. The dipyridinium salt of the trimeric sulfimide, which is derived from the ion (LXX), can be obtained (la) in a yield of 70% by reaction of amido-sulfuric acid chloride with pyridine at 20° ... 

The 5-acetyl derivative of (538) has been converted into the 5-NHj, 5-CO2H, and 5-CH2C02H compounds. From the amino-compound the 5-bromo-derivative was obtained upon diazotization, which upon treatment with potassium amide in liquid ammonia gave a mixture of the 4-amino-(major) and 5-amino-isomers. The compound (538) was converted into the iST-oxide, which upon nitration in sulphuric acid gave 4-nitrothieno-[2,3-Z>]pyridine 7-oxide. Nitration in acetic acid, on the other hand, gave the isomeric 5-nitro-derivative. Several reactions were carried out with these nitro-compounds. In a manner similar to that described for (538) and (539), the compounds (542)—(544) were prepared from 3-aminobenzo[6]-thiophen, 2-aminothieno[2,3- ]thiophen, and 5-aminobenzo[6]thiophen... 

The nitrate anion is a resonance-stabilized conjugate base of a strong acid. It is a weak base and should not induce an E2 reaction under normal conditions. On the other hand, the amide base derived from methylamine is a strong base (methylamine has a pK of about 25), and this powerful base should easily induce an E2 reaction. 

The oxidation of a ( )-flavanone with Tl(ni) nitrate, Pb tetracetate, phenyliodonium diacetate (PIDA), or [hydroxyl(tosyloxy)iodo]benzene in trimethyl orthofonnate affords the corresponding ( )-2,3-dihydrobenzo[h]furan derivative as a major product. The structures, including the relative stereochemistry, and a plausible mechanism of formation are reported. The preferred formation of a flavone from the ( )-flavanone by PIDA is explained by quantum-chemical calculations on the intermediate formed by the addition of this reagent to the enol ether derivative of the ( )-flavanone." Formation of mixed anhydrides by rapid oxidation of aldehydes, activated by pivalic acid, Bu OCl in presence of pyridine and MeCN is catalysed by TEMPO (2,2,6,6-tetramethylpiperidin-l-oxyl). The anhydrides can be converted in situ to esters, secondary, tertiary or Weinreb amides in high yield. Oxidation of the aldehyde to 2-propyl esters is also possible using only catalytic amounts of pivalic acid." ... 

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